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1.
Biomed Res Int ; 2015: 743051, 2015.
Article in English | MEDLINE | ID: mdl-25821817

ABSTRACT

Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.


Subject(s)
Etoposide/administration & dosage , Fibrosarcoma/drug therapy , Fibrosarcoma/pathology , Liposomes/chemistry , Milk/chemistry , Phospholipids/chemistry , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Camelus , Diffusion , Drug Synergism , Etoposide/chemistry , Female , Mice , Mice, Inbred BALB C , Treatment Outcome
2.
Int J Biol Macromol ; 76: 203-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25709021

ABSTRACT

The aim of the present study was to develop a novel liposomal formulation of thymoquinone (TQ) to treat fluconazole-susceptible and -resistant Candida albicans (C. albicans) infections. The liposomal preparation of TQ (Lip-TQ) was used against a fluconazole-susceptible or -resistant isolate of C. albicans. Various doses of fluconazole (0, 5, 10, 20 and 40 mg/kg) or free TQ or Lip-TQ (0, 1, 2 and 5mg/kg) were used to treat C. albicans infected mice. Mice were observed for 40 days post C. albicans infection, and their kidneys were assessed for the fungal load. Fluconazole showed anti-fungal activity against the drug-susceptible, but not against the -resistant isolate of C. albicans. Free TQ showed its activity against both fluconazole-susceptible or -resistant C. albicans, however, Lip-TQ was found to be the most effective and imparted ∼ 100% and ∼ 90% survival of mice infected with fluconazole-susceptible and -resistant isolates of C. albicans, respectively. Mice treated with Lip-TQ showed highly reduced severity of infection in their tissue homogenates. Therefore, Lip-TQ may effectively be used in the treatment of C. albicans infections, including those which are not responding to fluconazole.


Subject(s)
Antifungal Agents/pharmacology , Benzoquinones/administration & dosage , Candida albicans/drug effects , Candidiasis/microbiology , Drug Resistance, Fungal , Fluconazole/pharmacology , Liposomes , Animals , Antifungal Agents/administration & dosage , Candidiasis/drug therapy , Disease Models, Animal , Female , Liposomes/ultrastructure , Macrophages/drug effects , Macrophages/microbiology , Mice , Microbial Sensitivity Tests
3.
Cancer Epidemiol ; 38(6): 765-72, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25448084

ABSTRACT

In breast cancer cells, overexpression of human epidermal growth factor receptor 2 (HER2) increases the translation of fatty acid synthase (FASN) by altering the activity of PI3K/Akt signaling pathways. Cancer chemotherapy causes major side effects and is not effective enough in slowing down the progression of the disease. Earlier studies showed a role for resveratrol in the inhibition of FASN, but the molecular mechanisms of resveratrol-induced inhibition are not known. In the present study, we examined the novel mechanism of resveratrol on Her2-overexpressed breast cancer cells. The effect of resveratrol on the growth of breast cancer cells was assessed as percent cell viability by cytotoxicity-based MTT assay and the induction of apoptosis was determined by cell-death detection ELISA and flow cytometric analysis of Annexin-V-PI binding. Western immunobloting was used to detect signaling events in human breast cancer (SKBR-3) cells. Data showed that resveratrol-mediated down-regulation of FASN and HER2 genes synergistically induced apoptotic death in SKBR-3 cells. This concurrently caused a prominent up-regulation of PEA3, leads to down-regulation of HER2 genes. Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression. These findings suggest that resveratrol alters the cell cycle progression and induce cell death via FASN inhibition in HER2 positive breast cancer.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Stilbenes/therapeutic use , Anticarcinogenic Agents/administration & dosage , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Female , Humans , Resveratrol , Signal Transduction , Stilbenes/administration & dosage
4.
Int J Biol Macromol ; 65: 16-20, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24412154

ABSTRACT

Glycation plays an important role in various oxidative stress related diseases. Superoxide dismutase (SOD) constitutes an essential defense against oxidative stress. The damage caused by oxidative stress is exacerbated if the antioxidant enzymes themselves are inactivated by glycation. Thymoquinone (TQ) has been reported to have various pharmacological activities. Therefore, the glycation of SOD by glucose or methylglyoxal (MG) and its protection by TQ has been investigated. Incubation of SOD with glucose, MG or both at 37 °C resulted in a progressive decrease in the activity of the enzyme, and a parallel decrease in the amount of protein on SDS-PAGE gels for glucose incubated SOD and formation of high molecular weight aggregates for MG or both glucose and MG incubated enzyme. TQ offered protection against glucose or MG induced loss in SOD activity and fragmentation/cross-linking. The antiglycating activity of TQ appears to be better for mild glycating agents. It is also effective in protecting against strong glycating agents, more when the exposure time to the glycating agent is short. TQ has also earlier been reported to have anti-diabetic effects, and this along with the observed antiglycating effect makes it an effective compound against diabetes and its complications.


Subject(s)
Benzoquinones/pharmacology , Glucose/pharmacology , Pyruvaldehyde/pharmacology , Superoxide Dismutase/metabolism , Animals , Cattle , Drug Interactions , Glycosylation/drug effects , Oxidative Stress/drug effects
5.
Int J Health Sci (Qassim) ; 7(3): 333-40, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24533027

ABSTRACT

Chronic viral hepatitis is highly prevalent and creates a substantial burden to healthcare systems globally. The World Health Organization (WHO) estimates that over 350 and 250 million people worldwide are chronic carrier of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection respectively. These two diseases are the cause of significant global mortality and morbidity with approximately 1 million deaths each year attributable to them and their sequelae, liver disease and primary liver cancer. Although the efforts have been met with the long-lasting level of success and holds the promise for large reductions in disease burden in spite of the huge numbers of HBV infected population. The viral hepatitis has also been emerged as a leading public health concern and continues to be major disease burden in the Eastern Mediterranean. The WHO, estimates that approximately 4.3 million persons are infected with HBV in the Region each year. Saudi Arabia has been classified as a country with an intermediate prevalence of HBV showed up to 7% in Saudi children in late 1980s but declined to as low as 0.3% in 1997 since the introduction of universal vaccination of all Saudi children in 1989. In spite of this remarkable decline, the burden of decompensated liver disease secondary to hepatitis B is estimated to increase drastically in the next 40 years as the previously infected children start aging.

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